Use of the Erenna? Immunoassay Platform to Detect Pro-Inflammatory Cytokines in an In Vitro Cytokine Release Assay

摘要

Therapeutic antibodies (Abs) have proven to be efficacious in treating debilitating conditions including cancer and autoimmune diseases, but can trigger severe systemic inflammatory responses driven by cytokine release. Furthermore, toxicology studies have demonstrated limited predictive value for these phenomena even in nonhuman primates. Thus, development of improved in vitro assays using human material is necessary to evaluate the induction of these unwanted side effects, or gauging potential severity during preclinical evaluation. In an effort to develop such predictive safety assessments using human blood and tissue assays, Wolf et al., 2012[1] and Bailey et al., 2013 [2] have described a whole blood assay suitable for evaluating cytokine release in vitro. Human whole blood was incubated with monoclonal Abs known to induce severe systemic inflammatory responses in patients. The Erenna? Immunoassay system and kits were used to make highly sensitive, yet quantitative measurements of TNF-α, IL-2 and IL-6 levels. This enabled assessment of donor variability and -fold induction measurements, even when individual pro-inflammatory baseline cytokine levels were as low as 0.05 pg/mL.